The study of the inner nuclear membrane proteins is emerging as an exciting new field in biology because of the impact these proteins may have in development. We have recently shown that the inner nuclear membrane protein MAN1 can repress TGF-beta, BMP and activin signaling through its interaction with the Smad proteins. This is supported by studies showing that mutations in MAN1 that produce truncated proteins incapable of binding to Smad block TGF-beta superfamily signaling resulting in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Taking a biochemical and cell biological approach, this research will explore the function of MAN1 in the regulation of TGF-beta superfamily signaling, trying to elucidate the exact mechanism by which this inner nuclear membrane protein regulates TGF-beta superfamily signaling from the inner nuclear membrane.